Basket Trial Exploring the Efficacy and Safety of the Combination of Niraparib and Dostarlimab

NCT04779151 | Terminated Phase 2

• 2 other identifiers: 2020-002766-142020/3093
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

Treatment will consist of a PARP inhibitor (niraparib) monotherapy priming period (cycle 0; 21 days); an anti-PD-1 antibody (Dostarlimab ; TSR-042) will then be added from C1D1 every 21 days in combination for the first 4 cycles, and then every 42 days. Disease will be assessed every 2 cycles (6 weeks) from C3D1 by CT-scan (or MRI or bone scan, if relevant). Patients still under treatment after 1 year may have tumor evaluation spaced out every 3 cycles

Conditions

Urothelial Bladder Cancer; Gastric Adenocarcinoma; Gastro-oesophageal Adenocarcinoma; Head and Neck Cancer; Biliary Tract Cancer; Platinum-sensitive Urothelial Bladder Cancer; Clear Cell Renal Cell Carcinoma; Pancreatic Ductal Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  according to Response Evaluation Criteria In Solid Tumors v1.1 (RECIST v1.1)

  at 15 weeks

Study Arms (7)

1.A - Urothelial Bladder Cancer

EXPERIMENTAL

Drug: Dostarlimab; Drug: Niraparib

1.B - Gastric or gastro-esophageal junction adenocarcinoma

EXPERIMENTAL

Drug: Dostarlimab; Drug: Niraparib

1.C - Head and Neck Cancer

EXPERIMENTAL

Drug: Dostarlimab; Drug: Niraparib

1.D - Biliary Tract Cancer and pancreatic ductal adenocarcinoma (PDAC)

EXPERIMENTAL

Drug: Dostarlimab; Drug: Niraparib

1.E - Others: any histology, excepted breast cancer, prostate cancer or serous ovarian cancer

EXPERIMENTAL

Drug: Dostarlimab; Drug: Niraparib

Cohort 2 - Platinum-sensitive urothelial bladder cancer

EXPERIMENTAL

Drug: Dostarlimab; Drug: Niraparib

Cohort 3 - Clear Cell Renal Cell Carcinoma

EXPERIMENTAL

Drug: Dostarlimab; Drug: Niraparib

Interventions

Dostarlimab DRUG

Substance: immunoglobulin G4 (IgG4) humanized monoclonal antibody (mAb) that binds with high affinity to PD-1 Manufacturer: Tesaro Inc. Dose: 500 mg every 21 days for the first 4 cycles, followed by 1,000 mg every 42 days cycle (ie, Q6W)

1.A - Urothelial Bladder Cancer; 1.B - Gastric or gastro-esophageal junction adenocarcinoma; 1.C - Head and Neck Cancer; 1.D - Biliary Tract Cancer and pancreatic ductal adenocarcinoma (PDAC); 1.E - Others: any histology, excepted breast cancer, prostate cancer or serous ovarian cancer; Cohort 2 - Platinum-sensitive urothelial bladder cancer; Cohort 3 - Clear Cell Renal Cell Carcinoma

Niraparib DRUG

Substance: Inhibitor of poly-adenosine diphosphate \[ADP\] ribose polymerase (PARP) Manufacturer: Tesaro Inc. Dose: Flat-fixed dose (if \<77kg or platelets \<150,000 μL: 200mg; if \>/=77kg and platelets \>/= 150,000μL: 300mg)

1.A - Urothelial Bladder Cancer; 1.B - Gastric or gastro-esophageal junction adenocarcinoma; 1.C - Head and Neck Cancer; 1.D - Biliary Tract Cancer and pancreatic ductal adenocarcinoma (PDAC); 1.E - Others: any histology, excepted breast cancer, prostate cancer or serous ovarian cancer; Cohort 2 - Platinum-sensitive urothelial bladder cancer; Cohort 3 - Clear Cell Renal Cell Carcinoma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years.
• Patients must have histologically or cytologically confirmed progressive metastatic or recurrent solid tumor (as defined below for each tumor type). Diagnosis must be stated in a pathology report and confirmed by the physician investigator.
• Evidence of disease progression prior to trial entry.
• To be enrolled in this study, only the tumor types and settings described below are allowed:
• Cohorts 1 A-E: DNA repair deficiency, defined as bi-allelic loss-of-function alteration (mutation and/or deletion) in at least one of the following genes: ARID1A, ARID2, ATM, BARD1, BRCA1, BRCA2, BRIP1, CDK12, CHEK2, FANCA, IDH1, IDH2, NBN, PALB2, PBRM1, RAD51C, RAD51D, FANCA, NBN, RAD51, RAD54L, SMARCA4.
• Cohort 1A: Urothelial Bladder Cancer
• Patients must have received at least one line of prior platinum - based systemic therapy. No more than 3 lines of previous systemic therapy for metastatic disease are allowed.
• Relapse within 6 months of completion of adjuvant/neoadjuvant chemotherapy containing platinum-based regimen is considered as first-line therapy.
• Previous adjuvant/neoadjuvant chemotherapy is allowed, if completed more than 6 months prior to starting the first-line therapy.
• Patients must have platinum-sensitive disease defined as disease which reaches at least partial response after the last platinum chemotherapy line and the patient must have progressed at least 3 months after the last cycle of chemotherapy.
• Previous exposure to one line of anti-PD-1 or anti-PD-L1 is allowed, unless hyperprogression (Appendix 6) occurred on immunotherapy
• Cohort 1B: Gastric or gastro-esophageal junction adenocarcinoma
• Metastatic or recurrent gastric or gastro-esophageal junction adenocarcinoma that has progressed following at least 1 and maximum 2 prior therapies, by imaging modalities.
• Relapse within 6 months of completion of adjuvant/neoadjuvant chemotherapy is considered as first-line therapy.
• Previous adjuvant/neoadjuvant chemotherapy is allowed, if completed more than 6 months prior to starting the first-line therapy.

You may not qualify if:

• Participation in another clinical study with an investigational product simultaneously and/or during the last 4 weeks (excepting observational or non-interventional clinical studies).
• Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) 28 days prior to the first dose of study drug, or five half lives of the previous agent, whichever is the shorter.
• Participant has had radiation therapy encompassing \>20% of the bone marrow within 2 weeks prior to Cycle 0 Day 1; or any radiation therapy within 1 week prior to Cycle 0 Day 1.
• History of another primary malignancy within 5 years prior to Cycle 0 Day 1 except for:
• Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of study drug and of low potential risk for recurrence.
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
• Adequately treated carcinoma in situ without evidence of disease (eg, carcinoma in situ of the cervix, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ treated surgically with curative intent).
• Treatment with systemic corticosteroids or other immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and antitumor necrosis factor agents) within 2 weeks prior to Cycle 0 Day 1, or anticipated requirements for systemic immunosuppressive medications during the trial:
• o The use of inhaled corticosteroids for chronic obstructive pulmonary disease, mineralocorticoids for patients with orthostatic hypotension, low-dose supplemental corticosteroids for adrenocortical insufficiency and topical steroids for cutaneous diseases are allowed.
• Acute toxicities from previous therapies that have not resolved to Grade ≤ 1, with the exception of alopecia.
• Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE \> Grade 1.
• Participant must not have received a platelet transfusion ≤ 4 weeks prior to Cycle 0 Day 1.
• Participants must not have received colony stimulating factors (eg, granulocyte colony-stimulating factor, granulocyte macrophage colony stimulating factor, or recombinant erythropoietin) within 4 weeks prior to Cycle 0 Day 1.
• Participant has had any known Grade 3 or 4 anemia, neutropenia or thrombocytopenia due to prior chemotherapy that persisted \> 4 weeks and was related to the most recent treatment.
• Participant must not have any known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).

Sponsors & Collaborators

• Gustave Roussy, Cancer Campus, Grand Paris: lead

Study Sites (1)

Gustave Roussy

Villejuif, Val de Marne, 94800, France

Location

MeSH Terms

Conditions

Head and Neck Neoplasms; Biliary Tract Neoplasms; Carcinoma, Renal Cell

Interventions

dostarlimab; niraparib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Biliary Tract Diseases; Digestive System Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2021
• First Posted: March 3, 2021
• Study Start: April 7, 2021
• Primary Completion: February 25, 2025
• Study Completion: February 25, 2025
• Last Updated: December 1, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)